The objective of the proposed research is to develop reagents that will allow more informative imaging of breast tumors. Making the estrogen receptor (ER) protein the basis of tumor imaging might improve the accuracy of assessing the extent of metastasis. Consequently, treatment could be targeted accurately, and discomfort to the patient could be minimized. In support of this objective, the research plan is predicated on the synthesis of radiolabeled molecules (estrogens) that bind to ER with high affinity and selectivity. When bound to the relatively high amounts of ER in receptor-positive tumors, these estrogens would produce a radioactive signal that could be processed by positron emission tomography (PET) into a tumor image. A variety of known estrogens will be used as templates to design new potential estrogens containing gallium (Ga), one isotope of which decays by positron emission and could be detected by PET. The affinity and selectivity of non-radiolabeled Ga-containing compounds for ER will be measured in vitro. The in vitro stability of these compounds will also be determined. Promising Ga-containing estrogens will then be prepared in radiolabeled form and characterized for tissue distribution in rats, in order to confirm uptake by target tissues and the route of clearance from circulation. Finally, the most promising radiolabeled Ga-containing estrogens will be submitted to collaborators for in vivo evaluation as imaging agents of human breast tumors.